Bioactive NO meter

 was submitted as an idea in the contest -  "The best health idea" by Institute of the future.

Bioactive NO meter

NO (Nitric Oxide) is a radical gas and one of most important signaling molecules in the human body. Everything one does during ones life e.g., nutrition, physical activities, relaxation, entertainment, studies etc, is affecting NO availability. Thus NO measure reflects what is good or bad for us and what activities to adjust in order to achieve balance, health and longevity. An NO meter device (hand meter), which can measure bioactive NO levels through breath or skin's blood vessel dilation, will enable the user to design wisely the quality of his life.
Newer data show that indeed UVA exposure reduces human blood pressure by releasing nitric oxide metabolites from storage in the skin.
And more data on NO and skin such as - Novan Therapeutics is developing a topical nitric-oxide-based burn therapy.

by: Dina Ralt | Jul 31, 2010

506 people like this.

http://bodyshockthefuture.org/ideas.php?st=bioactive&reset_pe=1

Three days of vegetarianism, experimenting via social nets

The initial topic that we in CAMONI want to socially study is how the protein content in the diet affects type 2 diabetes? And is vegan diet relevant to this question?

The currently available literature indicates that vegetarian and vegan diets present potential advantages for the management of type 2 diabetes. Moreover, increased conformity to vegetarian diets protected against risk of type 2 diabetes even after lifestyle characteristics and BMI were taken into account.
Is it because the vegan diet does not contain animal protein? or maybe it's because on average vegan diets contain less protein?

It is the beneficial effects of gastric bypass surgery (GBP) to the diabetic that have led me to this suggestion, as this surgery reduces immediately the protein consumption.

As the incidence of obesity-induced type 2 diabetes continues to increase worldwide, medical studies indicate that surgery to reduce obesity can almost completely eliminate all manifestations of diabetes.
However please note that glycemic control is improved more after gastric bypass surgery than after equivalent diet-induced weight loss in patients with morbid obesity and type 2 diabetes mellitus.

What is the mechanism of this better metabolic response after GBP?

Several studies suggest that it might be related to the presence of amino acids (the bricks of proteins), e.g.
- Branched-chain amino acids decreased after GBP, but not after dietary intervention
- Five branched-chain and aromatic amino acids had highly significant associations with future diabetes.

As diets high in animal protein are associated with an increased diabetes risk, it is suggested that consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk.

All these findings indicate that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

This is the reasoning for our social net study - If your are diabetic Type 2 and care to try, please become vegetarian for 3 days and measure how it affects your sugar levels.
Please comment here or at facebook how it affected you.

We plan to collect data from many net surfers and see if preliminary conclusions can be deduced. If we trace protein level diabetic effects, it will be interesting to see if we all (men/women, young/old, lean/obese) respond similarly.

IMPORTANT - For a vegan diet please eliminate for 3 days all animal proteins (eggs, meat, fish, milk and its products) and replace it with equal calories from nuts, almonds legume or beans (do not add - bread, sugar or sweets).
Please be carefull to avoid hypoglycemia.
Do not forget to make sure that your physician acknowledges your selected diet.

No milk today...

It’s about a year now that I abstain from milk and milk products. As it has affected (positively) my wellbeing so dramatically, I strongly recommend to generalize the concept - It is worthwhile to search ones roadblocks for health, in situations where ones efforts to heal do not result in contentment.

Losing weight is my personal issue of life (also my scientific field of study), so for years I eat “right” as well as smartly exercise daily, and yet it was milk abstinence that enabled the 17kg weight loss this year. In the chart below (my "excess kg") you may see that in the previous year I have lost 5 kg with the same exercise & diet but with milk and its products (cottage cheese and yogurts). So milk abstinence enabled over 3 times faster weight loss. Pls note that the no-milk diet is not poorer in calories as instead I eat a lot of almonds which have higher caloric value.

It has also (even before the weight loss was manifested) balanced my morning blood sugar levels (I am diabetic II) and now my HbA1c is balanced - 5.6 (it used to be 6.8 regardless of my very low carbohydrates consumption).

One of my articles on obesity, defines 2 urges to eat - the need to eat as well as satiety, are regulated by these two unrelated urges. One urge is activated by our daily energy expenditure and the other by the need to accumulate energy for the future (activated by the degree of our bodily worry). I have also explained how satiety of the second urge is critical for a healthy weight loss. A US team indeed found levels of white blood cells were highest in men who were unfit and overweight. High levels of white blood cells can be a sign of inflammation/body worry.

Indeed I’ve found that I show Lactose Intolerance and I guess this was a main body-worry which inhibited my health as well as my weight loss. It is intersting to note that in the ESHG 2009 meeting, a study demonstarted that the variant responsible for lactose intolerance among Europeans was also associated with higher BMI.

But milk is not the only generator of worry, e.g. exposure to insecticide may cause such a worry and thus can play role in obesity… as well as other chemical exposures.

Milk damage might not be related only to Lactose Intolerance, e.g. it was shown to be related to cancer progress via its N-glycolylneuraminic acid.

And more:

1- French study demonstrated increases in weight with high dairy calcium intakes in normal-weight women, and positive relations between milk consumption and waist circumference change in overweight women.

Am. J. Clinical Nutrition, 2008; 88(5), 1248-1255

2- Milk products appear insulinotropic.

Am. J. Clinical Nutrition, 2001; 74(1), 96-100

3- High intake of various food groups such as red meat, fried potatoes, cheese, and cottage cheese is associated with risk of type 2 diabetes.

Diabetes Care, 2009, 32, 263-268

4- In kids (age 9-14), dietary calcium and skim and 1% milk were associated with weight gain, but dairy fat was not.
Arch Pediatr Adolesc Med. 2005;159:543-550

5- Children in Crete with insulin-dependent diabetes mellitus, consumed more dairy products and less meats and cereals.
Ann Nutr Metab. 2008 Aug 19;52(4):308-314

6- The majority of current evidence from clinical trials does not support the hypothesis that dairy consumption aids in weight or fat loss.

Nutrition Reviews, 2008, 66(5),272-297

7- A family diet rich in dairy products during childhood is associated with a greater risk of colorectal cancer in adulthood.

Am. J. Clinical Nutrition, 2007, 86(6), 1722-1729

8- The intake of dairy products may be associated with an increased risk of prostate cancer.

Am. J. Clinical Nutrition, 2005; 81(5), 1147-1154

Cancer Epidemiol Biomarkers Prev 2008;17(4):930–7

9- Milk-the promoter of chronic Western diseases

Med Hypotheses. 2009, 72(6), 631-639

10- Cow's-Milk-Free Diet as a Therapeutic Option in Childhood Chronic Constipation.

J. Pediatr. Gastroenterol. Nutr. 2010, May 4 e-pub ahead of print

and last, milk may also help bacteria survive against low levels of antibiotics.

It is worth a trial to avoid milk consumption …

Did you ever try the Paleo diet?

Chinese 5 Elements Mark Johnson's Questionnaire

If the question sounds a lot like you, put +2
If it is somewhat like you, put +1
Put a 0 if it is neutral
-1 if it is not much like you
-2 if it is nothing like you


If you hate questionnaires and refuse to do it, you are more than likely a "Wood" person!

Phase IAre you a natural born initiator?
Do you have problems with authority figures?
Do you suffer from migratory pains?
Do you act assertively and confidently?
Does other people's slowness and clumsiness irritate you?
Do you like struggling against great odds to prove to others you can do it?
Are you frequently doing something or going somewhere?
Do you have high blood pressure?
Have you often been told you don't compromise much?
Do you have to be the first and best?
Does confinement and sitting quietly drive you crazy?
Do you get frequent muscle cramps?
Do you like to make the rules and then break them?
Are you passionate about everything you do?
Do you pioneer new trails wherever you go?
Do your nails alternate between hard and thick and dry and brittle?
Are you impatient with uncommitted people with no direction?
Are you afraid to show vulnerability?
Have you ever had tendonitis?
Do you love speed and adventure?
Do you tend to manipulate people and situations to get what you want?
Is controlling your anger one of your biggest problems?
Do you find any kind of restraint insufferable?
Do you do your best work under pressure?


Phase II
Would you describe yourself as an introspective "loner"?
Do you have an exaggerated sex drive?
Is the search for TRUTH a prime motivator in your life?
Do you hate superficiality in people?
Are you creative, imaginative and original?
Are you modest and fear being in the limelight?
Are you self contained and self sufficient?
Is deterioration of teeth and gums a problem?
Do you seek the deep mystery in everything?
Are you out of touch with your emotions?
Do you suffer with backaches frequently?
Are you tactless and even rude occasionally?
Do you have a very penetrating and critical mind?
Do you hate waste and conserve everything?
Is stick-to-ativeness one of your strongest virtues?
Do you have hardening of the arteries?
Is it hard for you to share with others?
Do you suffer with isolation and loneliness?
Are you afraid of loosing yourself in others?
Are you considered enigmatic and eccentric by your friends?
Do you have remarkable powers of concentration?
Are you awkward in social circumstances?
Do you have trouble conforming?
Have you had kidney or bladder problems?
Are you watchful and objective with other people?


Phase III
Do you spend a lot of time and energy consciously seeking the divine?
Do you have an enlarged or weak heart?
Are you charismatic?
Do you have an extreme aversion to pain?
Do you love drama, performing and being in the limelight?
Are you often spontaneous?
Do you get sores on your tongue and around your mouth?
Can't say NO to anyone?
Do you tend to be more sensual than your friends?
Do you love to give your opinion?
Do you fear separation above all else?
Are you clever on your feet?
Do you desire fulfillment more than almost anything?
Do you bore easily with the dull and ordinary?
Do your cheeks turn red easily?
Could you be described as extravagant?
Are you bright and scintillating at social gatherings?
Do you have eczema?
Do you have trouble with boundaries?
Is the need for intimacy a strong motivation with you?
Does sharing come easily?
Are you mostly optimistic and enthusiastic about life?
Are you strongly empathetic?
Do you suffer from anxiety and insomnia?


PHASE IVAre you a "law and order' person?
Do you hold righteousness and virtue in high regard?
Are rituals important to you?
Do you have stiff joints and muscles?
Is chaos your enemy?
Do you have no time for nonsense?
Do you hold very precise standards?
Are you really sensitive to temperature changes?
Are you intolerant of disorder and dissonance?
Is your skin and hair really dry?
Do you fear intimacy?
Do you have a strong aesthetic sense?
Does carelessness in others drive you up a wall?
Are you considered cool, dispassionate and distant?
Do you have a tight chest with dry coughing?
Are reason and high principles your guiding light?
Are you a little too strict and nit-picky?
Do you have refined tastes?
Have you been called self-righteous?
Do you have a lot of moles and warts?
Is social involvement on the bottom of your list of important things to do?
Do you have sinus problems?
Does your constant self control drive your spontaneous friends crazy?
Are you into changing other people?
Do you suffer from constipation?


PHASE VDo you see yourself as a service oriented person?
Are you working on being more self-reliant?
Do your friends often use you as a negotiator?
Is bloating and water retention a problem?
Do you struggle with inertia and feel "stuck" sometimes?
Does nurturing come easy to you?
Are you haunted with self-doubt?
Do you like to be in charge, but not in the limelight?
Does your efficiency leave something to be desired?
Does your need to be accommodating result in conformity?
Do you often go through an identity crisis?
Is a need to belong strong in you?
Do you suffer with muscle tenderness?
Are you referred to as a "peacemaker" by your friends?
Do you regard loyalty as being one of the more important traits in a person?
Are you quite conservative in your thinking?
Do you have a strong need to be needed?
Are you often involved in everybody else's business?
Do you suffer with swollen glands and other lymphatic disorders?
Would you like things more predictable because things are changing too fast?
Do you tend to be overly protective?
Do unrealistic expectations leave you disappointed much of the time?
Do you try to be all things to all people?
Is there a deep "emptiness" in the pit of your stomach?
Do you have a squarish, solid physique?

__________________________

Phase I is the WOOD phase
Phase II is the WATER phase
Phase III is the FIRE phase
Phase IV is the METAL phase
Phase V is the EARTH phase

Now add up each phase by subtracting the negatives from the positives and
see which ones have the highest numbers. Often you will have a phase or
phases that are negative. This is OK. The phase with the least amount of
negatives is your dominant phase. We are all a mixture of these phases so
it is the PROPORTION between them that is important. More than 25 points
between the highest and lowest is a sign of imbalance.

For instance from dominant to weak might look like this...
WOOD +18, FIRE +9, EARTH -9, METAL -10, WATER +5 This is a WOOD person
with a weak EARTH phase. To balance them, strengthen Fire
or...WOOD -25, FIRE -16, EARTH -13, METAL 0, WATER -9, This is a METAL
person with a week WOOD phase. To help them, strengthen their WATER.
or...WOOD +6, FIRE +4, EARTH +1, METAL -1, WATER -2, This person is
balanced and all they need do is maintain that balance!

CAMONI - a smart social health website

Health, is a private issue as well as a collective circumstance, thus network phenomena appear to be relevant to health upkeep. This was well established in evaluating smoking cessation (1) obesity spread (2) as well as happiness expansion (3).
Along with its social benefit, the net is an intelligent source of information, which is essential for medical issues in health websites that must be trusted.
Information is needed as even minimum medical knowledge is dramatically lacking (4). For example, a community-wide study in New York found that nearly 28 percent of all visits to the pediatric emergency department could have been replaced with a more cost-effective Internet doctor's "visit" (5). It is interesting to note that nowadays, patients doubt doctors' advice when it conflicts with online info (6).

So what’s the hindrance? Despite the clarity of its essentiality, social health websites evolve much slower than popular social sites. We assume that the prevention is partly due to the required novel attitude/approach in health management. Novel not only to the patients but also to the physicians and caretakers.

These considerations were in the root of designing Camoni, the first Israeli health and medical social network (in Hebrew).
The Camoni (means in Hebrew: “like me”) project was initiated by Prof. M Shani, and its main focus is the wellness of the person with chronic ailment as well as his environment.
The disorders that Camoni targets initially include heart failure, diabetes, blood pressure disorders, kidney disorders, obesity, eating disorders, spinal cord injuries, and chronic pain.

The Camoni website supplies both medical expertise (knowledge) and communication routes. To establish the trust of the Israeli surfer, Camoni offers the web-surfer, leading Israeli medical experts in chronic diseases. All of the experts are well known and are members of leading hospitals and medical institutes throughout Israel. In joining Camoni, they agreed to be available for the Camoni members and patients everyday of the year.
As a part of their contribution to the community of Camoni, the network's experts publish news and articles in the areas of their expertise - some of which might become main parts of the discussions throughout the Camoni blogs and forums .

One of the notions for our public health cure is, that prevention (7) is an ultimate key to ease many chronic conditions, such as diabetes, obesity, heart ailments and more. As sociability (8) is a strong tool we try to approach it in many ways. In the net via forums, blogs, webmail, discussion groups, virtual meeting support groups etc. But also outside the net via familiar routes to the non-internet patient, these routes like music (9), art or social connections (10) will be recorded in the Camoni website and slowly will be used to enable non-surfers to get familiar with the net.
Camoni aims to constantly evolve, improve and offer its users the newest communication tools for social networking in order to create a friendly and most useful virtual health environment.

Until recently, it was recommended that in order to be healthy, one needs to exercise and to eat vegetables. Today one needs also to surf (11).

Does NO metabolism play a role in the effects of vegetables in health?

Nitric oxide formation via the reduction of nitrites and nitrates.
Ralt, D.
The Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel
Medical Hypotheses, 2009, 73(5), 794-796

Abstract
A recent attribution of vegetables to human health stems from their effect on the gasotransmitter nitric oxide (NO). This commentary proposes that a major reason for this attribution is that vegetables are rich in nitrates. Recent research has shown that nitrites and nitrates are not only inert end-products of NO oxidation. In addition, they can be recycled back to bioactive NO and this pathway is an important alternative to the classical L-arginine-NO-synthase pathway.
Various chronic ailments, e.g. diabetes, obesity, high blood pressure, are symptomatic of NO bioavailability. Because NO deficiency is metabolically complex, natural nitrate-rich nutrients, such as green leafy vegetables, can improve these chronic ailments via the alternative nitrate-NO pathway.
This commentary implies an added value for vegetables in enhancing health such as cardiac health and in lowering the risks of maladies such as diabetes.

Introduction
Fruit and vegetables rich diets has been associated with lower risk of chronic diseases including cancer and cardiovascular disease and provide beneficial effects that can be attributed to a variety of protective agents [1, 2, 3]. In this commentary, the therapeutic attributes of vegetables will be discussed mainly in terms of their nitrates and nitrites content as a source for nitric oxide (NO) [4, 5, 6, 7].
The past decade has witnessed a significant increase in the interest of biologists in NO. This highly reactive free radical, first considered only a noxious air pollutant, plays a vital role in many biological events including regulation of blood flow, immunity and neurotransmission [8].
Recent data demonstrate that NO is not only a paracrine substance. It has been shown that enzymatic generation of NO in the heart is capable of modulating remote physiological actions and cell signaling [9]. NO was also shown to affect the computational ability of the brain; it regulates information transmission across neurons [10]. Extensive data from studies on NO signals, on relaxation/stress processes and on health, supports a view of an NO net, serving as a body coordinator [11, 12].

The necessity of NO for body functions is suggested by the fact that its deficiency is correlated with various chronic ailments such as, obesity [13], diabetes [14], hypertension [15], pulmonary hypertension [16], osteoporosis [17] and old age [18]. Supplementing NO levels is helpful and thus 5-phosphodiesterase inhibitors (e.g. Viagra), have a potential protective role in chronic ailments as coronary artery disease [19, 20]. It is also not surprising that though helpful, the response rate to NO related drugs as Viagra is lower in diabetics [21].

The problematic nature of chronic ailments is the occurrence of an extended, not necessarily hazardous, condition (see the following elaboration on obesity). Thus, while temporary deficiency of NO may not pose a dramatic risk, a long term NO deficiency becomes hazardous.
NO bioavailability in the body depends on the rate of its synthesis and metabolism. Though arginine is a main precursor for the NO synthesis [22], it has lately been established that mammalian nitrate and nitrite reduction can also contribute to NO biogenesis [23, 24]. This commentary recommends an increase in consumption of nitrate-rich vegetables to prevent NO shortage and its consequential ailments. These nitrate-rich nutrients support health via reduction of nitrites and nitrates to NO [25]. Though beyond the scope of this commentary, it is worth mentioning that vegetable consumption has many nutritional benefits, these include supplementing precursors not only to NO but also to other gasotransmitters such as H2S [26, 27].

Discussion
This section is composed of 3 parts:
- Description of a chronic ailment (obesity) and its NO deficiency.
- Curing NO shortage via nitrates and nitrites supplementation.
- Nitrate rich vegetables indeed improve chronic ailments.

Obesity and NO deficiency
Obesity, which begins as simple overweight, over time becomes a malady correlated with ailments such as heart disease and diabetes [28]. NO deficiency may explain this pattern [29]. There are a number of studies that support this idea.
First, NO and citrulline are decreased in obese juveniles when compared to normal weight juveniles, and are negatively correlated with body weight. Arginine (the NO precursor) however, is increased in obese juveniles and is positively correlated with body weight [13]. Therefore, whereas low levels of NO are correlated with obesity,
it is not the lack of arginine that limits NO bioavailability.
Second, another study demonstrated that excess of fat in the body results in excess of the leptin hormone, which in turn, can lower the levels of bioavailable NO [30].
In addition, it is interesting to note that caloric restriction, without malnutrition, extends life span in a range of organisms [31] and that there is an NO link between caloric restriction and mitochondria [32].

Until the last century, obesity was a rare and impermanent condition and a transient lowered NO communication capacity was not necessarily unhealthy. Today, when obesity is mostly irreversible, prolonged inhibited NO bioavailability is hazardous and can account for the numerous maladies associated with obesity [28].

The reduction of nitrites and nitrates
Increasing the sources of NO, may therefore, contribute to the health of the obese even in the absence of losing weight. When arginine oxidation to NO is prohibited, alternative routes for NO production are effective - the reduction of nitrites and nitrates [33].
Nitrate and nitrite are important alternative sources of NO in especially, but not exclusively, hypoxic states [34]. Following are some examples; The intermittent hypoxia improved glucose tolerance [35]. Nitrite therapy augments ischemia-induced angiogenesis [36], nitrate reduction is emerging as a regulator of physiological functions and tissue responses to myocardial infarction or stroke [23] and brief elevations in plasma nitrite trigger a concerted cardioprotective response [37]. In addition to supplementation of NO compounds in acute situations, it is also effective in improving the urogenital system and skeletal health [38].
As suggested by Tamaki [39], dietary nitrite-derived NO generation may serve as a backup system when the NO synthase/L-arginine-dependent NO generation system is compromised.

Best Nitrite and Nitrate Food Sources
Some of the best nitrate-rich foods are lettuce, spinach, beetroot [6] and fruits such as pomegranates [40, 41]. Accumulating data shows that these foods improve various chronic ailments. Following are some examples; Beetroot reduces high blood pressure [42], green leafy vegetable consumption is linked to lower risk for diabetes in women [3], nitrate rich vegetables were shown to decrease the oxygen demand during exercise [43], pomegranate juice consumption by patients with carotid artery stenosis decreases carotid IMT and systolic blood pressure [44] and indeed NO produced from nitrite plays important roles in limiting post-ischemic tissue injury [45].
Because increasing substantially the daily consumption of vegetables is not simple [46, 47, 48], it seems worthwhile to spread the trend of drinking vegetable juices [49] when dealing with chronic ailments.

It is interesting to note that the Dunhuang scrolls dating to approximately 800 AD, suggested that nitrite and nitrate were used by the Chinese to relieve chest pain and reduce cold in the hands [50].

Conclusions
Regulation of NO function is showing itself to be a complex event that maladies are associated with its disruption.
Here, it is proposed that vegetables can at least partly, reverse these effects by increasing NO generation via nitrate and nitrite. This explains how encouragement of daily consumption of extra vegetables supports good health.
Vegetables can be considered a natural “drug” with sustained release of low-dose nitrite into the circulatory system, alternative source to the L-arginine pathway to NO.

List of abbreviations
NO - nitric oxide
IMT - intima-media thickness


References
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- after publication relevant articles:
* Food sources of nitrates and nitrites: the physiologic context for potential health benefits
Am J Clin Nutr. 2009, 90(1), 1-10
* The University of Leicester team believe nitric oxide may change the way we think and hear.
http://news.bbc.co.uk/2/hi/health/8116194.stm
Nitroglycerin Bioactivation
http://www.jbc.org/cgi/content/abstract/284/30/19878
http://www.sciencedaily.com/releases/2009/08/090819125042.htm

A novel obese therapy - reversed (reduced) NO production

The two major topics that attract my scientific interest are obesity and the routes of NO -nitric oxide (the above links summarise my previous studies).
NO, as I have suggested, enabled the initial physiological communication of multicellular organisms and serves now as a support communication system in all living organisms.
It was thus no wonder for me to read the recent Austrian study, which showed that obesity reduces the bioavailability of NO. The studied obese juveniles revealed highly significant alterations in the NO pathway. NOX and citrulline were decreased in obese compared to normal weight juveniles and negatively correlated with body weight. Arginine was increased in obese juveniles and positively correlated with body weight. Is the arginine accumulation related to the arginine paradox? Or mainly to the inhibition of NOX synthesis?
Int J Obes 2008 32: 826-831
I would like to suggest that the decrease in NO bioavailability in the obese (as well as in diabetics or others) is the result of a “savings” strategy…Resources are directed from activeness to accumulation (fat) and lowering the “primordial” communication system may be associated with this lower physiological tempo.
This might remind also aging… and indeed aging is also associated with an impaired bioactivity of NO. It is no wonder that obesity and aging have a lot in common… See also the effect of adipose tissue reduction on lifespan.

This article is meant to point a fault in the obesity strategy (e.g., see below how smart is the Sirt1 startegy). It is true that the obese are trying to accumulate a reservoir for the future, but is it essential that they also lower the NO communication system?
I would try to explain such an evolutionary logic by suggesting that obesity was in the past (before our century) rare and impermanent and maybe a transient lowered communication capacity was even helpful…
Today when obesity is permanent, such prolonged inhibited communication is hazardous and might be the reason for the numerous maladies associated with obesity.
We could thus assume that enhancement of the NO resources might contribute to the health of the fat person even when they do not lose weight.
This reminds me of the resveratrol, found in red wine, which keeps obese mice healthy, and of course the SirT1 which regulates energy metabolism and responds to caloric restriction in mice. It does so smartly, by repressing UCP2 , or via promoting fat mobilization ...see also the recent PNAS Sirt1 article... as well as the new data on the essential CLOCK protein that regulates the body's circadian rhythms and works in balance with the Sirt1...
Is NO signaling in the biological clock, impaired in the obese?
Recent data form Denmark indeed show that human adipose tissue contains Sirt1 and the expression of Sirt1 can be regulated by calorie restriction just as in other species. Interesting... lean women had more than twofold higher Sirt1 expression in subcutaneous adipose tissue compared to obese women...Is this related to NO?

So what can we do to improve wellness in spite of obesity? or in other words, how can we improve the NO availability?
L-arginine supplementation does indeed improve insulin sensitivity and endothelial function in obese type 2 diabetic patients…However I want to mention that it was associated with higher postinfarction mortality… and moreover, arginine was anyway increased in obese juveniles...

I would like to suggest a novel wellness therapy; induction of the reverse route - NO formation via nitrites and nitrates… or maybe through citrulline who is also decreased with obesity.

Nitrate and nitrite are important alternative source of NO to the classical L-arginine-NO-synthase pathway, in particular (but not only) under hypoxic states.
Note that intermittent hypoxia indeed improved glucose tolerance… nitrite therapy indeed augments ischemia-induced angiogenesis... and a role for mammalian nitrate reduction in regulation of nitrite and NO homeostasis as well as: Human endothelial cells bioactivate organic nitrates to nitric oxide.
Hypoxia can also assist wellness via preventing the producion of the toxic peroxynitrite...
It is interesting to note that documents (Dunhuang scrolls) dating to approximately 800 AD, suggested that nitrite and nitrate were used by the Chinese to relieve heart pains and cold in the hands.
I am a cautious person and thus I tend to recommend mainly wise nutrition (rather than food additives) and physical activity... please also consult your physician before applying any measure.
It is rather obvious that we should recommend nitrate-rich vegetables such as spinach, lettuce, radishes or beetroot or fruits like pomegranate.
Nitrate rich vegeatbles such as beetroot indeed reduces blood pressure ... in another experiment it was shown that green leafy vegetable consumption was linked to lower risk for diabetes in women and in another it was shown to decrease the oxygen demand during exercise.
We could also recommend Red wine, which (besides its other qualities, such as its antioxidants) was shown to promote the reduction of nitrite to NO.
Small amounts of polyphenol-rich dark chocolate improved formation of nitric oxide.
On Viagra we could talk as well, but please be moderate…

As for physical activity, a rather hypoxic is the body building…I wonder if my usual recommendation for body building (obesity, diabetes or old age) contributes to this reverse NO formation as well and thus makes this type of physical activity a major contributor to wellness.