I will admit that at one point I’ve tried all these health supplements and even swore by some of them at one time. However, they are not consistent with my current ideology of first doing no harm, and then incorporating good things. This article will cover curcumin, resveratrol, carnitine, fish oil and nitric oxide supplements. As you will see from the graphic below, there are a lot of ways for something to fail, and many conditions must be satisfied for it to be considered good.
I’ve written extensively about mild stress (mental and physical exercise, sun radiation) being potentially good for the body when used appropriately. I get the feeling that many supplements are mildly stressful to the body, and it is for this reason, why they “work.” For this reason, even if they do “work,” they should probably be cycled, as you would cycle exercise or grueling mental exercise giving the body a chance to rebuild and strengthen from the mild stressors. When I say cycle, I mean something like 4 days on 3 days off. Or two weeks on, one week off.
Mild stressors may increase pituitary activity or adrenal activity leading to a false sense of well-being while they suppress thyroid hormone output. Or mild stressors may suppress the immune system leading to what seems like less inflammation.
Popularized by Dr Oz, this compound from turmeric root, is marketed as an anti-inflammatory, anti-everything-bad supplement. Curcumin is the principal curcuminoid of the popular South Asian spice turmeric, which is a member of the ginger family. The curcuminoids are natural phenols that are responsible for the yellow color of turmeric. This is a common ingredient in Indian food. That said, food dosages of “stressful” plants may be the right amount of stress whereas a concentrated supplement may not be. Being a root (not a seed or herb), turmeric should overall be considered safe for mild use if cooked properly.
Curcumin doesn’t pass the test of not interfering with thyroid hormone. The study below shows that it may stress the body causing it to create MORE thyroid hormone in youth, when the body still possesses the youthful ability to do so in response to stress. However, as the organism ages, levels free thyroid hormone T3 dropped significantly.
“The study was conducted on 3- and 18-month-old male Wistar rats. The experimental rats were treated daily for 30 days by gavage with 100 mg/kg b.w. of curcumin. There were observed age-related changes in morphology and endocrine function of the thyroid. It was increase in the percentages of large follicles (increase in FSH) and significant decrease in FT3 level in 18-month-old rats in comparison to 3-month ones. Curcumin treatment lead to significant increase in FT3 and FT4 levels in 3-month-old experimental rats, but the level of FT3 significantly decreased in 18-month-old rats after curcumin administration. Our results show that curcumin activity depends on the functional condition of the rat thyroid which changes with age. This compound exerts stimulatory influence on the secretory function of the thyroid gland in young rats, but has rather weak antithyroid activity in old animals.”
Considering most of the people considering using this supplement are old, I recommend not using it. The increases in FT3 in younger rats may be caused by increasing pituitary activity and TSH which is not the desirable mechanism for doing so.
From a cytotoxicity standpoint, one study shows that curcumin may play a role in increasing radical oxygen species and the release of cytochrome c. Cytochrome c is also an intermediate in apoptosis, a controlled form of cell death used to kill cells in the process of development or in response to infection or DNA damage. Cytochrome c binds to cardiolipin in the inner mitochondrial membrane, thus anchoring its presence and keeping it from releasing out of the mitochondria and initiating apoptosis. Therefore, it appears curcumin may increase controlled cellular death, which may be why it is effective in klling unhealthy cancer cells. However, most of us are not trying to get rid of cancer, we are trying to live with healthy cells.
Because there are so many conflicting studies, I consider it’s mechanism of efficacy unclear and recommend not using concentrated Curcumin supplements.
Also popularized by Dr Oz along with Red Wine, Resveratrol is a compound contained in grape skins, seeds and vines as a natural plant defense against fungus and parasites. As common sense would say, if this is toxic to fungus and parasites, why would we consider it healthy? Granted when found in naturally occurring quantities such as in wine and grapes, maybe its mild toxicity can make the body stronger through the process of stress and hormesis. However, many people are taking concentrated, very high doses of this supplement.
Resveratrol is anti-thyroid.
The study below shows that reserveratrol does interfere with thyroid activity, and increases TSH while decreasing both T4 and T3 for a double-negative effect. It also decreased thyroid perixodase (TPO) activity which is responsible for breaking off iodine for combination with tyrosine for production of thyroid hormones T3 and T4.
“The present study showed that: the effect of 3 doses of trans-resveratrol (200, 400, and 800µg /kg/day) orally for 4 weeks significantly increased thyroid weight and relative thyroid weight. Trans-resveratrol (200µg/kg/day p.o.) for 4 weeks significantly increased serum TSH level and decreased both serum T4 and T3 levels. Trans-resveratrol (200µg/kg/day p.o.) for 4 weeks significantly inhibited microsomal TPO activity.”
Resveratrol is, with no surprise, cytotoxic according to studies.
Perhaps this is why it is an effective for killing cancer cells. Unfortunately as the study below shows, it is also cytotoxic against stable cell-lines. It is also effective at killing viruses as seen in the following paragraph. However, killing viruses is only useful if you have a virus. Having a strong immune system by using basic nutrients (Zinc, C, E, Selenium) is a better way to defend against viruses.
“The cytotoxic action is exerted towards a stabilized cell-line (3T6) as well as a tumor-line (HL60). Resveratrol is cytotoxic and inhibits, in a dose dependent fashion, the synthesis of polyomavirus DNA in the infected cell. Furthermore, this inhibition is observed at non cytotoxic concentrations of the drug. Our data imply that cyto-toxicity may be attributed to the membrane damage caused by the drug and that the transfer of polyomavirus from the endoplasmic reticulum to the cytoplasm may be hindered. In conclusion, the cytotoxic and antiviral properties of resveratrol make it a potential candidate for the clinical control of proliferative as well as viral pathologies. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed it’s ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A.”
Lipid peroxidation is a marker of significant cell death and is significantly increased after administering resveratrol.
However, even low doses of RSV induced an increased reactive species production at both treatment times. While being diminished within 24 h, RSV induced an increase in the SOD activity in 120 h. The cellular damage was substantially increased at 24 h in the 50 μM RSV-treated group, as indicated by the high lipoperoxidation, which may be related to the significant cell death and low proliferation. Paradoxically, this cellular damage and lipoperoxidation were considerably reduced in this group after 120 h of treatment while the surviving cells proliferated.
Resveratrol suppresses metabolism and increases Nitric Oxide.
In a recent study, to determine whether resveratrol would slow the heart rate and lower the body temperature in mice, those metabolic indicators were depressed by resveratrol for one day, but then returned to normal. The endurance of the mice on a treadmill was reduced by the resveratrol treatment (Mayers, et al., 2009). This sounds similar to Gilbert Ling’s frog that’s heartbeat never returned to original strength after a spell of living with a depressed metabolism.
Resveratrol also promotes the formation of Nitric Oxide and estrogen. This causes chromosomal damage (Banerjee and Banerjee, 1994; Kulling, et al., 1999) which contributes to cancer and possibly to birth defects.
3) Carnitine (GPLC or Acetyl L Carnitine)
Carnitine is an amino acid found in red meat. It is marketed as a fat loss supplement because it increases lipolysis (the conversion of fat to sugar). While that does sound good for weight loss, using fat for energy is very inefficient and hard on the body, and makes you prone to storing more food as fat as it represents a primitive, slow metabolism. The people who have written extensively about it being good have experienced adrenaline highs. They may not have experienced adrenaline lows (where tissue is no longer sensitive to adrenaline) yet, but they will. All fatty acids are deficient in oxygen (two oxygen atoms per molecule) so using them for energy automatically creates more lactic acid than CO2. CO2 is produced in greater amounts by the use of sugar (typically six or more oxygen atoms per molecule depending on the saccharide size) for energy.
While it is naturally found in red meat which I do recommend eating somewhat regularly, at least red meat contains other nutrients (zinc, vitamin A, copper, B6) that help support glucose metabolism unlike taking a single amino acid supplement which solely supports fatty acid metabolism.
“Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, to obtain usable energy via the citric acid cycle. In some organisms, such as fungi, the acetate is used in the glyoxylate cycle for gluconeogenesis and formation of carbohydrates. Fatty acids must be activated before binding to the carnitine molecule to form ‘acylcarnitine’. The free fatty acid in the cytosol is attached with a thioester bond to coenzyme A (CoA). This reaction is catalyzed by the enzyme fatty acyl-CoA synthetase and driven to completion by inorganic pyrophosphatase.”
Beyond inefficient energy production, there may be a link between dietary consumption of carnitine and atherosclerosis which is associated with heart attacks. When certain species of intestinal bacteria were exposed to carnitine, they produced a waste product, trimethylamine, which is transformed in the liver to trimethylamine N-oxide (TMAO). TMAO may be associated with atherosclerosis. The presence of large amounts of TMAO-producing bacteria was a consequence of a long-term diet rich in meat.
Relying on fatty acid metabolism and carnitine for energy production can negatively affect bones, which require continuous reconstructive and efficient metabolic functions of osteoblasts for maintenance of bone mass.
Carnitine is anti-thyroid.
In addition, carnitine may negatively affect the transport of T3 and T4 into cells – which makes sense as fatty acid metabolism and free fatty acids inhibits glucose metabolism by reducing insulin sensitivity, L-carnitine has been found to act as a peripheral antagonist of thyroid hormone action. In particular, L-carnitine inhibits both triiodothyronine (T3) and thyroxine (T4) entry into the cell nuclei.
Carnitine increases transport of fatty acids into cells.
Paradoxically, children with carnitine deficiency may have increased free fatty acid concentrations and hypoglycemia. This makes sense if you understand that carnitine transports fatty acids into cells for energy production. The key is to not have high free fatty acids to begin with by making sugar a principle part of your diet to suppress adrenaline and ensuring you have adequate levels of vitamin B3 (niacinamide). The reduction of free fatty acids will increase your glucose sensitivity and improve your metabolism without use of carnitine.
As Darwin pointed out, being able to adapt by switching energy sources is important to the survival of the organism, for this reason, I recommend short and medium chain saturated fatty acids (coconut, dairy) as a principle part of the diet as they do not interfere with glucose metabolism to the same degree of unsaturated fatty acids and have higher levels of oxygen per molecule. This way when you do have to rely on fatty acids for energy, more CO2 per gram of fatty acid is created.
4) Fish Oil
Because fish oil is high in omega 3, it is believed to improve insulin sensitivity, brain health, heart health, and reduce inflammation. As I’ve written about lipid peroxidation in other posts, I don’t have much else to say on it. It should not be a surprise that an oil designed to keep fish from freezing solid in cold water oxidizes when exposed to heat, but some people are not satisfied with such a simplistic answer so here are some studies.
“The original “essential fatty acids” were linoleic, linolenic, and arachidonic acids. Now that the toxic effects of those are coming to be recognized, new “essential fatty acids,” the omega-3 fatty acids, including those with long chains, found in fish oils, are said to make babies more intelligent, to be necessary for good vision, and to prevent cancer, heart disease, obesity, arthritis, depression, epilepsy, psychosis, dementia, ulcers, eczema and dry skin.” – Ray Peat
Because most fish oils are already oxidized prior to consumption, lipid peroxidation cannot be mitigated by Vitamin E supplementation
“The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eighty men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.”
In a separate study, it was shown that levels of thiobarbituric acid-reactive substances (an index of lipid peroxidation) and antioxidants in the liver and kidney and the serum levels of triacylglycerol were highest in fish oil-fed mice showed increased levels of thiobarbituric acid-reactive substances compared with soybean oil or olive oil fed mice.
“The weak bond makes them enormously susceptible to attack by reactive oxygen species (ROS) generated elsewhere in the body. Because of the five double bonds in EPA and six double bonds in DPA, these metabolites are highly sensitive to temperature.”
Fish Oil Does Nothing for Heart Health and Increases Prostate Cancer
There are numerous resources proclaiming fish oil helps with heart health and prevents prostate concern. These dreams were shattered by a group in Italy, a country that would likely benefit from increased fish consumption. Though, most Meditaranean fish are warm water fish so their fat content is lower anyways.
“The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil’s EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy) released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention—both primary and secondary.”
“Another major 2013 setback occurred when fish oil’s DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) analysis by Brasky et al.b Another monumental failure occurred in 2013 whereby fish oil’s EPA/DHA failed to improve macular degeneration. In 2010, fish oil’s EPA/DHA failed to help Alzheimer’s victims, even those with low DHA levels.”
In particular, DHA, with its 6 double bonds, contains 5 bis-allylic bonds and is therefore 320 times more susceptible to oxidative attack, that is, becoming rancid, than monounsaturated oleic acid (18 : 1), which has no bis-allylic hydrogens in its chain. A saturated fat membrane containing just 5% DHA (fish oil) is 16 times more susceptible to peroxidative damage . Fish oil’s DHA is 7 times more susceptible to peroxidative damage than LA (Parent omega-6), the most significant fatty acid by both weight and functionality in the cell’s bilipid membrane. This fact should cause the medical community great concern.”
Fish Oil Reduces Inflammation by Suppressing the Immune System
There is lots of literature out there on how fish oil reduces inflammation. The problem is they don’t take into account what is causing the inflammation in the first place. Omega 6 fatty acids from the seed oils convert into the inflammatory arachidonic acid and prostaglandins. Studies have shown that high levels of prostaglandin D-2 in the scalp are partially responsible for causing hair loss. The bright side of fish oil is that it does interfere with the formation of prostaglandins. However, so does vitamin E and so does aspirin without the negative side effects. In fact, the highly oxidized fish oil (becomes saturated) may be the thing that is responsible for this action.
As Ray Peat notes:
“With just a normal amount of vitamin E in the diet, cod liver oil is certain to be highly oxidized in the tissues of a mammal that eats a lot of it, and an experiment with dogs showed that it could increase their cancer mortality from the normal 5% to 100%. Although fish oils rapidly destroy vitamin E in the body, some of them, especially the liver oils, can provide useful vitamins, A and D. In studies comparing fish oil diets with standard diets, these nutrients, as well as any toxins besides fatty acids (Huang, et al., 1997; Miyazaki, et al., 1998) in either type of oil, should be taken into account, but they seldom are.“
High doses of fish oil might also reduce the immune system’s activity, reducing the body’s ability to fight infection. This is a special concern for people taking medications to reduce their immune system’s activity (organ transplant patients, for example) and the elderly.
Indeed, in a study done on mice attempting to prove the anti-inflammatory and immune supporting effects, researches found the mice were more susceptible to induced bacterial infections following high doses of fish oil.
“Contrary to expectations, DHA (2.25–6%) induced severe colitis and adenocarcinoma formation. Increased severity of colitis in DHA fed mice was associated with a CD8+ driven response to bacterial infection. These results suggest that DHA supplementation in immune-associated diseases like IBD should be approached with caution.”
Fish Oil is toxic to the body as it depletes vitamin E and is destroyed by young people, but not be the elderly.
In a experiment done on 15 younger (22-35) women and 10 older (51-71) women, women received six capsules of fish oil and 6 IU of vitamin E. Blood was collected before and after 1, 2 and 3 months of supplementation. All women had increases in EPA and DHA in their blood. Elderly women had a 10-fold increase in EPA and a 2.5-fold increase in DHA. Younger women only had an increase 8 and 2 fold respectively. This implies that younger people are more suited to getting rid of the toxic effects of fish oil. This is also perhaps due to a less leaky gut and lower endotoxin in younger people. After three months of supplementation, vitamin E levels were significantly lower in the younger women.
5) Nitric Oxide Supplements
Popularized by body builders for giving a “pump” and by men looking to improve erection strength, Nitric oxide has been related to many good things in the mainstream. The main supplements for increasing Nitric Oxide are arginine and citrulline, but is not limited to just those two as some herbs and foods also increase Nitric Oxide levels. Citrulline is found in high quantities in watermelon, but probably not high enough to do damage unless you religiously eat watermelon. High consumption of arginine is associated with herpes type break outs and acne that are counteracted by appropriately increasing lysine consumption. This is another reason whole food sources of protein are better because they do not allow for such imbalances.
Citrulline is more effective at increasing Nitric Oxide levels because it bypasses the liver and is not broken down by arginase. I’m not sure if this makes it more “safe” or not.
Nitric oxide is increased by an unhealthy gut loaded with endotoxin.
“Niacinamide protects mitochondrial respiration from many of the age-related factors that can damage mitochondria and decrease energy production. Lipopolysaccharide, the bacterial endotoxin, increases the production of the free radical nitric oxide, leading to the secretion of inflammatory mediators and the suppression of energy production by the mitochondria. These effects are blocked by niacinamide (Fukuzawa, et al., 1997). Calorie restriction also protects mitochondrial respiration, in yeasts (Lin, et al., 2002) and rats (Broderick, et al., 2002)
Estrogen has a similar effect on keratinocytes. Resveratrol, nitric oxide, and estrogen, unlike niacinamide, suppress mitochondrial respiration. Resveratrol inhibits the formation of progesterone (Chen, et al., 2007), which is synthesized in mitochondria.”
Nitric oxide is involved in inflammation.
NO is involved in the pathogenesis of inflammatory disorders of the joint, gut and lungs. Therefore, NO inhibitors represent important therapeutic advances in the management of inflammatory diseases.
Nitric Oxide is Cytotoxic and Decreases Levels of Endogenous Antioxidant Enzymes
The body produces endogenous enzymes such as catalase, glutathione peroxidase and superoxide dismutase. Lots of people talk about eating sprouted foods containing these, but I’m not sure those significantly increase the levels in the body due to destruction by stomach acid. The best way to increase them it to eat a diet that supports their formation endogenously.
“The effect of NO on the endogenous antioxidant enzymes (AOEs) catalase, glutathione peroxidase (GPX), and CuZn- and Mn-superoxide dismutases (SODs) was investigated in rat cells. The 24-h treatment with SNAP, a NO donor, decreased the activities and the protein levels of catalase, GPX, and Mn-SOD in a dose-dependent manner. Alternatively, the activity and the protein level of CuZn-SOD were increased. PTIO, a NO scavenger, blocked the effect of SNAP. Moreover, the treatment with another NO donor, or with a combination of LPS and IFN-gamma, which induce excessive production of NO, also significantly reduced AOE activities in a manner similar to that seen with SNAP treatment. The compounds/enzymes that inhibit the production of NO (PTIO) blocked the effects of LPS and IFN-gamma on the activities of AOEs. These results suggest that alterations in the status of AOEs by NO may be the basis of NO-induced cytotoxicity in disease states associated with excessive NO production.”
Nitric Oxide is Anti-Thyroid
And most importantly, high levels of nitric oxide are anti-thryoid. The thyroid produces thyroperixodase, an endogenous enzyme that assists the chemical reaction that adds iodine to a protein called thyroglobulin, a critical step in generating thyroid hormones. Thyroid hormones play an important role in regulating growth, brain development, and metabolism. Unfortunately, nitric oxide reduce iodide uptake by thyroid cells reducing TPO and TG expression.
Nitric oxide (NO) induces morphological and functional alterations in primary cultured thyroid cells. Cells were treated with the NO donor sodium nitroprusside (SNP) for 24-72 h. SNP (50-500 micromol/L) reduced iodide uptake in a concentration-dependent manner. The inhibition of iodide uptake increased progressively with time and matched nitrite accumulation. SNP inhibited thyroperoxidase (TPO) and thyroglobulin (TG) mRNA expression in a concentration-dependent manner. These findings favor a long-term inhibitory role of the NO/cGMP pathway on parameters of thyroid hormone biosynthesis. A novel property of NO to inhibit TPO and TG mRNA expression is supported.