AS WE AGE, INFLAMMATION BECOMES THE KEY CONSUMER OF NAD+ AND LEVELS DROP (54,67).
Decreasing systemic inflammation is likely the most effective thing you can do to minimize NAD+ consumption so it is available for other purposes.
Did you know that fat cells secrete cytokines that increase systemic inflammation, disease and aging? (73,74,75).
- MSM – Methylsulfonylmethane
- Micronized Curcumin
- Boswellia Serrata
- Silibinin (from Milk Thistle)
health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity
Pre-treatment with MSM, prior to exhaustive exercise, prevented the over-stress of immune cells 
As a therapeutic agent, MSM utilizes its unique penetrability properties to alter physiological effects at the cellular and tissue levels. Furthermore, MSM has the ability to act as a carrier or co-transporter for other therapeutic agents, even furthering its potential application
MSM was also shown to be effective in reducing arthritis pain when used in combination with boswellic acid 
MSM is effective at reducing other inflammatory pathologies in humans as well…
SILIBININ (AKA SILYBIN, SILIMARIN, OR MILK THISTLE)
Silibinin, the main component of silymarin, has been proposed as a nutraceutical for the treatment of NAFLD. In this study, we aimed to identify whether silibinin may influence the NAD⁺/SIRT1 axis. To this end, C57BL/6 mice were fed a high fat diet (HFD) for 16 weeks, and were treated with silibinin or vehicle during the last 8 weeks. HepG2 cells were treated with 0.25 mM palmitate for 24 h with silibinin 25 µM or vehicle. HFD and palmitate administration led to oxidative stress, poly-(ADP-ribose)-polymerase (PARP) activation, NAD⁺ consumption, and lower SIRT1 activity. In mice fed the HFD, and in HepG2 treated with palmitate, we consistently observed lower levels of phospho-AMPKThr172 and phospho-acetyl-CoA carboxylaseSer79 and higher levels of nuclear sterol regulatory element-binding protein 1 activity, indicating de novo lipogenesis. Treatment of mice and HepG2 with silibinin abolished oxidative stress, and inhibited PARP activation thus restoring the NAD⁺ pool. In agreement with preserved NAD⁺ levels, SIRT1 activity and AMPK phosphorylation returned to control levels in mice and HepG2. Our results further indicate silibinin as a promising molecule for the treatment of NAFLD.
Bioavailability Issues & Ways to Overcome Them
Silybin, the main active component in the standardized milk thistle extract Silymarin, has poor bioavailability. Only around 20–50% of it gets absorbed from the gut. This is because silybin can’t dissolve in water that makes most of the stomach and gut fluids. What’s even worse is that stomach acid can also degrade it, so sometimes it won’t even reach the gut.
There are many ways to overcome its bioavailability issues.
- Berberine increases the bioavailability of silybin and the two act together in synergy [R]
- Other flavonoids increase its absorption [R]
1) Milk Thistle Protects Liver
Fatty Liver Disease
A combination of Milk thistle’s active compound, Silybin, phosphatidylcholine, and vitamin E over 1 year improved non-alcoholic fatty liver disease (NAFLD) in a clinical trial of 179 people. It reduced liver enzymes, insulin resistance, and liver scarring with no serious side effects. Some of the included Hepatitis C+ participants included in the trial experienced the same benefits [R, R].
However, the active ingredients can reach higher blood levels in people just with fatty liver disease than in those with Hepatitis C. After being absorbed, silybin is secreted into the gut with bile. People with Hepatitis C can’t absorb silybin again and “recycle” it, which lowers its blood concentration [R].
Overall, silybin from milk thistle improves fatty liver disease, even in people who also have Hepatitis C. But those with Hepatitis C may need higher doses (2.1g/day of silybin) to compensate for the liver damage that affects bioavailability [R].
Alcoholic Liver Disease
Silymarin (450 mg/day) increased the master antioxidant glutathione and reduced oxidative stress in red blood cells in a clinical trial of 60 people with alcoholic liver disease after 6 months. It didn’t affect liver function or enzymes in this study, though [R].
Protecting the Liver from Drugs and Toxins
Milk thistle may protect the liver from drugs and toxins [R].
In animals, silymarin and silybin protected the liver against damage from alcohol, toxins (carbon tetrachloride and thallium), chemotherapy drugs (cisplatin), Tylenol (acetaminophen), radiation, iron overload, and the poisonous mushroom death cap (Amanita phalloides) [R+, R].
In a clinical trial of 50 children with leukemia, milk thistle protected the liver and reduced damage from chemotherapy drugs after 1 month [R].
In a woman with leukemia, silymarin (800 mg/day) reduced the side effects of chemotherapy drugs and protected the liver over 4 months [R].
Milk thistle doesn’t protect the liver from all drugs. For example, it didn’t protect the liver from anti-tuberculosis drugs in a study of 380 people. On the contrary, it even slightly increased the risk of liver damage [R]
Most mushroom poisonings worldwide are from a mushroom called “death cap”. Milk thistle is the number 1 antidote for death cap poisoning, given as IV silybin (oral silybin doesn’t work). It saved lives in over 90% of 1500 cases in the US, which is better than any other antidote. It should be given within 48h to prevented severe liver damage and increase survival [R, R, R].
2) Milk Thistle is an Antioxidant
In a clinical trial of 40 people with type 2 diabetes, Silymarin (420 mg/day) over 45 days enhanced antioxidant defense, boosting total antioxidant capacity and key enzymes such as glutathione and SOD. It also reduced the inflammatory marker CRP[R].
According to cellular studies, milk thistle acts as an antioxidant by:
- Activating the body’s detox hub, Nrf2 [R].
- Blocking the master inflammation pathway called NF-kB [R].
- Increasing mitochondrial health and activating Heat Shock Proteins, which protect cells and tissues under stress [R, R].
- Increasing sirtuins, which help conserve energy, reduce aging and inflammation [R].
- Neutralizing free radicals, chelating free iron and copper [R].
- Blocking harmful enzymes that increase oxidative stress [R].
3) Milk Thistle Reduces Inflammation
Tightly tied to its antioxidant activity, milk thistle is a strong anti-inflammatory. It blocks most pathways that trigger or worsen inflammation in the body.
In pregnant mice with infections, its active compound silybin reduced inflammation in the brain and preterm births. It lowered inflammatory substances (IL-6, IL-8, PGE2) and enzymes (COX-2) and gene expression (MMP9) [R].
4) Milk Thistle May Reduce Autoimmunity
Once of the reasons why women are more susceptible to Th17-dominant autoimmune diseases is because estrogen is involved in maintaining a healthy immune response. In order to reduce the Th17 inflammatory response, estrogen receptors need to be activated. Estrogen normally does this, but its levels drastically fall in women after menopause [R].
Milk thistle can activate estrogen receptors and reduce autoimmunity. In a study of healthy people and those with rheumatoid arthritis, silybin had a beneficial epigenetic effect (increasing ER-beta and miR-155). It binds to estrogen receptors in white blood cells, reduces the autoimmune response and inflammatory cytokines (IL-17 and TNF-a) [R].
5) Milk Thistle Protects the Brain
Silybin reduced brain injuries and brain inflammation in mice with infections [R].
It prevented memory loss and improved learning in rats by reducing oxidative stress in the brain. This active compound from milk thistle reduced damage in the brain’s memory hub, the hippocampus. The hippocampus is part of the limbic system, which controls emotions and the stress response. This region is often inflamed in people with brain fog [R].
It also had a beneficial epigenetic effect in mouse brains. Silybin increased the expression of BDNF, which helps make new brain cells, and of tyrosine receptor kinase B (TrkB), which helps make and strengthen new connections in the brain in response to BDNF [R].
Silymarin reduced symptoms of Parkinson’s disease and damage from stroke in mice. It neutralizes free radicals in the brain, blocks the master inflammation pathway NF-kB, and reduces damage to brain cells. It lowers the activation of the brain’s immune cells (microglia), which may help prevent many neurodegenerative diseases [R, R].
6) Milk Thistle May Help with Diabetes
Milk thistle can be combined with berberine for blood sugar control. In one study of 85 people with type 1 diabetes, this combination reduced the insulin doses needed to keep blood sugars in check and also lowered blood fats [R]
In a trial of 60 people with diabetes and alcoholic liver damage, Silymarin (600 mg/day) improved insulin resistance and oxidative stress while reducing the need for insulin injections over 1 year [R].
7) Milk Thistle Improves Metabolic Syndrome
Milk thistle is a promising natural alternative for people with metabolic syndrome [R].
In 136 obese people with type 2 diabetes, a combination of berberine and silymarin improved all harmful disease markers after 6 months. It reduced fasting blood glucose and insulin, improved insulin resistance, raised HDL, reduced total, LDL cholesterol, and triglycerides. It also reduced the BMI, waist circumference, and belly fat [R]
In 51 people with type 2 diabetes, silymarin (600 mg/day) didn’t only reduce blood sugars but also lowered total cholesterol, LDL, triglycerides, and liver enzymes (AST and ALT) [R].
In another study of 40 people with type 2 diabetes, Silymarin (420 mg/day) improved insulin resistance, blood triglycerides, and increased the beneficial HDL cholesterol over 45 days. Plus, it reduced the inflammatory marker CRP and increased antioxidants [R, R]
In 137 people who didn’t tolerate high doses of lipid-lowering statin drugs, silymarin with berberine (~200/1200 mg/day silymarin/berberine) improved blood sugar, insulin, and didn’t worsen blood fats when the drugs were stopped [R]
In cells, milk thistle can block Pancreatic Lipase, an enzyme that breaks down fats in the gut and helps absorb them. By blocking this enzyme, milk thistle may reduce the amount of fat absorbed from the diet [R].
8) Milk Thistle Protects the Heart
One way that milk thistle can protect the heart is indirectly, by lowering blood fats that contribute to hardening of the arteries and heart disease. Milk thistle reduced triglycerides, total and LDL cholesterol and increased HDL cholesterol in several clinical trials [R, R, R]
But it may also lower blood pressure by reducing inflammation. In one study, silymarin was applied to the immune cells of pregnant women with high blood pressure. It blocked all the major inflammatory pathways (TNF-a, IL-1b, NF-κB) [R]
Milk thistle prevented heart injury and disease in rats. It also protected muscle cells from injury by restoring healthy activity in the mitochondria. Plus, milk thistle can turn on genes that reduce inflammation and protect the cells from damage (Bcl-2) [R, R].
9) Milk Thistle May Fight Cancer
In one clinical trial, 60 people with benign polyps in the colon (which often develop into colon cancer) took a herbal blend with milk thistle, a flaxseed antioxidant, and oat fiber for 2 months before colonoscopy. The combination increased estrogen receptors in the colon, which helps kill these “pre-cancerous” cells and prevent colon cancer [R]
Milk thistle has low bioavailability, but standardized extracts can still reach the blood and cancer tissues. In 12 women with breast cancer, a combination of silybin and phosphatidylcholine (2.8 g/day) for 4 weeks before surgery was safe and built up in the breast cancer tissue more than in healthy tissue [R]
In one study, even high doses (up to 13 g/day) of a special milk thistle formulation (Silybin-phytosome) over 4 weeks was safe in 13 people with prostate cancer [R]
Milk thistle could also be added to sunscreen to naturally protect against skin cancer, as it prevented skin damage in animal studies [R].
- Increasing cancer cell suicide (apoptosis)
- Preventing cancer cells from spreading and invading other tissues
- Stopping cancers from making blood vessels that help them survive
- Blocking the abnormal division of prostate, ovarian, breast, lung, skin, bone, and bladder cancer cells
- Reducing the expression of inflammatory genes
10) Milk Thistle Improves Bone Health
Milk thistle (silymarin) improved bone healing and increased bone mineral density in mice with bone fractures [R].
Milk thistle may compensate for low estrogen levels after menopause, as the drop in estrogens increases the risk of osteoporosis. It prevented bone loss and increased the activity of cells that help mineralize and rebuild bones in postmenopausal mice [R].
In bone cells, milk thistle boosted the activity bone-forming cells and blocked bone-degrading cells [R].
This product is not intended to diagnose, treat, cure, or prevent any disease.