Lupus Encyclopedia

Updated 4/10/21

Why do people with lupus think it is unsafe to take melatonin?

It is because there are outdated websites and patient education pages that state this. It even occurs on highly-acclaimed sites such as the Mayo Clinic.

How can the Mayo Clinic be wrong?
Most likely: there are tons of patient education pages that were produced a long time ago.
There is probably no one who polices and up dates them.
Certainly the doctors are way too busy to do this: they are taking care of patients and doing research.

Theoretically, melatonin may improve the immune system in lupus
     and other autoimmune diseases

- One problem in lupus is that there are lower numbers of important white blood cells called Tregs (regulatory T-cells).
- Tregs help to normalize the immune system and prevent overactivity.
- With less Tregs, bad B-cells that make dangerous lupus autoantibodies (such as anti-dsDNA) can live a very long time (and even forever, "immortal").
- Melatonin does effect the immune system. One of the things it can do is increase these important Tregs that could be helpful in lupus and other autoimmune diseases
- The 2013 research article referenced below by Lin GJ et al and the 2019 article by Zhao et al go into detail about this

What happens to lupus mice when they are given melatonin

- When melatonin is given to female mice that are prone to getting lupus, it prevents them from getting lupus!
- This was shown in a 2010 study by Zou LL et al and another in 2008 by Jimenez-Caliani AJ et al (referenced below)

How about humans?

 - There are no studies of using melatonin in people with lupus.
- This is a huge reason why it is incorrect to tell people with lupus not to use melatonin. There is no evidence to support that recommendation.
- However, there is a study in people with rheumatoid arthritis (a related autoimmune disease).
     - Melatonin did NOT worsen rheumatoid arthritis in these patients (Maestroni et al, referenced below)

_________________________________________________________________________

BOTTOM LINE:

I do not ask my patients with lupus to avoid melatonin.
There is actually more evidence that it may be beneficial rather than harmful.
Lupus patient education websites should remove their recommendations to avoid melatonin.
​These sites and pages are outdated.

REFERENCES:
​https://pubmed.ncbi.nlm.nih.gov/31345729/
​https://pubmed.ncbi.nlm.nih.gov/23727938/
https://pubmed.ncbi.nlm.nih.gov/18507713/
https://pubmed.ncbi.nlm.nih.gov/20706659/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2432495/

Other facts about DHEA:

- DHEA stands for DeHydroEpiAndrosterone
- It is produced by the adrenal glands
- It is made from cholesterol (yes, cholesterol is a necessary part of our body)
- It is both a steroid and a hormone
- It has both female hormone activity and male hormone activity
- It is used by the body to produce estrogen (female) and testosterone (male)
- It is the most abundant hormone in the human body
- Many lupus patients have lower than normal DHEA levels. This is what started the research to use it for treatment
- The prescription form of DHEA goes by the brand name Prasterone. The FDA would not approve its use for lupus due to the clinical trials not being strong enough to support FDA-approval.

Thanks to Kelli Roseta of More Than Lupus for publishing "Ask Dr. T"

​- Maintain a regular sleep schedule; get up and go to bed the same time daily even on non-work days and holidays.
- Reduce stress in your life.
- Get exposure to light first thing in the morning to set your biological clock. Consider using a non-UV source of light exposure such as the Philips goLITE or the Miroco non-UV light.
- Exercise daily; mornings and afternoons are best. Don’t exercise right before bedtime.
- Avoid naps late in the afternoon or evening.
- Finish eating two to three hours before bed; a light snack is fine, but avoid foods containing sugar as it can stimulate the mind and interfere with falling asleep.
- Limit fluids before bed to keep from getting up to urinate throughout the night.
- Avoid caffeine six hours before bed.
- Do not smoke; if you do, don’t smoke for two hours before bed; nicotine is a stimulant.
- Avoid alcohol two to five hours before bed; alcohol disrupts the sleep cycle.
- Avoid medicines that are stimulating (ask your doctor).
- Avoid stimulating mind activities for a few hours before bed (reading technical articles, listing tasks to do, trouble-shooting, paying bills, etc.).
- Have a hot bath one to two hours before bed; it raises your body temperature and you will get sleepy as your temperature decreases again afterward.
- Keep indoor lighting low for a few hours before bed.
- Establish a regular, relaxing bedtime regimen (aroma therapy, drink warm milk, read, listen to soft music, meditate, pray, do relaxation/breathing exercises).
- Ensure your sleeping environment is quiet and comfortable (comfortable mattress and pillows; white noise like a fan; pleasant, light smells).
- If pets ever wake you, keep them outside of the bedroom.
- Use the bedroom only for sleep and sex; never eat, read, or watch TV in bed.
- Never keep a TV, computer, or work materials in your bedroom.
- Go to bed only when sleepy.
- If you can’t go to sleep within fifteen to twenty minutes in bed, go to another room and read something boring under low light, meditate, pray, listen to soft music, or do relaxation/breathing exercises until sleepy.
- If you have dry mouth problems, use a mouth lubricant such as Biotene Mouth Spray before you go to bed.

​Anti-Inflammatory Diet for Autoimmune diseases

This is the latest handout I give to my own patients. It has information from some of the latest medical research regarding foods to eat and avoid in order to hopefully decrease inflammation in the body. It talks about anti-inflammatory foods to eat, which to avoid, intermittent fasting, prebiotics (such as resistant starches), and probiotics. As per the Lupus Secrets, do this along with taking your medications, exercising regularly, getting at least 8 hours of sleep each night, and protecting yourself from ultraviolet light.

If you find this helpful, please share with others. 

There is growing evidence that eating a diet high in foods that decrease inflammation, while avoiding, or minimizing foods that increase inflammation, can help autoimmune diseases such as lupus and rheumatoid arthritis. One of the latest studies from the University of California, San Diego Medical Center showed that rheumatoid arthritis patients had significantly better disease control when sticking to this type of diet. Lupus studies show that diets rich in omega-3 fatty acids and low in omega-6 fatty acids can help disease activity in people with lupus as well as mice with lupus. Lupus mice also have better disease control when they eat a diet rich in "resistant starches." Resistant starches as discussed in the probiotics section below.  Note that the Mediterranean diet has many of these anti-inflammatory recommendations. You can find information on the internet or ask your doctor for a copy of our Mediterranean diet. 

Should you avoid nightshade plant foods? Avoid gluten?

Controversial diet changes

Some experts recommend the following changes, while others do not due to insufficient data). One reason I am skeptical of this is because tomatoes are rich in lycopenes, a strong anti-oxidant (so, it seems like they should be healthy rather than harmful). This is one of those areas that needs more study.:

Decrease the intake of nightshade (solanaceae) vegetables (tomatoes, eggplant, potatoes) if you believe this. Personally, I would still eat them. However, like with any foods, if you predictably flare by eating them, then you should avoid them.

Decrease the intake of gluten products (instead of wheat bread and pasta, switch to rye bread, corn tortillas, quinoa/beet/bean/ or chickpea pasta). However, most experts recommend avoiding gluten only if you truly have celiac sprue (gluten hypersensitivity). 
*** NOTE: These recommendations are not for people who have celiac sprue, gluten-sensitive enteropathy, or gluten sensitivity. Though these are lower in gluten than wheat breads and pastas, some (such as rye) can contain gluten.

The microbiome in autoimmune diseases:

We have trillions of bacteria living on and inside of us; all together it is called our "microbiome." The insides of our intestines and gastrointestinal tract contain the largest immune system organ of our body, and the constant interactions of the microbiome bacteria and our immune system can either cause beneficial effects when we have good (beneficial) bacteria in our microbiome, or abnormal effects that can actually cause increase autoimmune disease. Studies of the microbiome and autoimmune diseases such as RA and lupus are in its infancy. Many studies have been performed in animals with lupus and RA, and smaller studies have been done in humans. We have so much to learn, but we do realize that having good bacteria that decrease autoimmunity, and getting rid of bad bacteria that increase autoimmunity are very important. Here are some recommended practices that you can do that may help you.

1. Take great care of your oral health! Poor dental health can actually cause RA and make it worse, and now there is evidence that it can do the same with lupus (in fact, one study showed that treatment of periodontal disease in lupus patients improved their lupus disease activity significantly.  Make sure and do the following:
     - Floss every day (flossing picks are very handy to use)
     - Brush twice a day
     - If you have dry mouth, talk to your doctor about how to improve the much needed saliva in your mouth to increase good bacteria and decrease the bad.
     - DO NOT SMOKE! (this is why smokers lose their teeth at a much younger age than nonsmokers)
     - Chew on gum that contains xylitol (or use Xylimelts, or use mouth wash that contains xylitol eg TheraBreath Maximum Strength)
     - Get your teeth cleaned every 6 months (every 3-4 months if you have dry mouth)

2. Improving the microbiome in the gut has less medical evidence behind it. It is probably important to do, but we lack good large studies in humans. However, increasing the amount of resistant starches in your diet may be beneficial.
     - Resistant starches include cold oat meal (eg overnight oats), potato starch, green banana starch, potatoes that are cold after being cooked, and lentils
     - These types of starches aren't digested well until the get into the large intestine where they begin to ferment. Then beneficial bacteria use these starches for food and interact favorably with the immune system and also decrease the numbers of bacteria that cause immune system problems
     - Including a serving of resistant starches in your diet daily is probably a good idea.

​Probiotics in autoimmune diseases:

Probiotics are live bacteria, touted to have beneficial effects by living within our intestinal system and interacting with our immune system. While probiotic supplements have been shown to have some benefit for gastrointestinal problems (such as irritable bowel syndrome), no human studies have proven benefit for autoimmune disorders yet. In fact, in animal research, some autoimmune disorders improve with some probiotic organisms while others actually worsen. Therefore, we do not recommend any probiotic supplements.  Probiotics may be beneficial for the microbiome as above.

However, many foods are rich in natural probiotics, and thus far, there are no studies suggesting that any of these foods make autoimmune disorders worse. Therefore, you may want to consider the possibility of consuming a daily portion of any of the following probiotic rich foods:

Probiotic rich foods
Greek yogurt
Kefir
Kimchi (fermented, nonpasteurized)
Kombucha tea
Miso soup (warm, not boilded)
Tempeh 
Sauerkraut, fermented, nonpasteurized (warm, not cooked too hot)
Fermented, nonpasteurized pickles
Dark chocolate (just a little, and NOT milk chocolate)
Cold green peas on salads
Olives
Natto (very healthy, but takes an acquired taste)
Beet kvass
Fermented beets
Cottage cheese containing live cultures (eg "Good Culture" and "Horizon organic")
Soft, aged cheeses (especially gouda; but also parmesan, cheddar and swiss; the longer the aging, the higher the probiotic content)


References:
Bustamante MF, et al. Contemp Clin Trials Commun 2020
Guma M, et al. Trial of diet to improve RA and impact on the microbiome. Presented at ACR Convergence 11/9/2020.
Zegarra-Ruiz DF, El Beidaq A, Iñiguez AJ, et al. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. Cell Host Microbe. 2019;25(1):113-127.e6. doi:10.1016/j.chom.2018.11.009

Diet used in 2020 rheumatoid arthritis study above
Slides above and below posted with permission of Dr. Monica Guma, MD (principal investigator of this research study. The reference is at the bottom) 

At the American College of Rheumatology (ACR) meeting NOV 2020, Dr. Monica Guma of UCSD reported results of using an anti-inflammatory diet in the autoimmune disease, rheumatoid arthritis (rheumatoid arthritis). She used the diet posted above.

This is pertinent for lupus patients because lupus is also an autoimmune disease. Note that there are some anti-inflammatory diet studies in lupus mice and lupus humans that show positive effects. However, we need larger, bigger studies. This study is a step in the right direction (even though it is with RA instead of lupus).

She chose motivated RA patients. They stayed on their medications as well. They followed the above diet. They had to have active RA to enter the study. Disease activity was measured 2 weeks before the study, at the start of the study, then 2 weeks later. The bacteria in their stool (microbiome) was also measured!

Below is an example of a typical day of eating:

How did the RA patients do on this anti-inflammatory diet?

After 2 weeks on the diet, there was improved disease activity (overall) with less tender and swollen joints.
Disease activity (measured by a research tool called the CDAI) was significantly decreased.
Below are the results after 2 weeks on the diet.

​For the scientific minded... note the great "p values" for some of these measurements on the right.

What did their gut microbiome do in response to the anti-inflammatory diet?

After 14 days, those RA patients who did better (had lower RA disease inflammation) on the anti-inflammatory diet ended up with a greater diversity of their microbiome. This suggests that the diet influenced their gut bacteria types as well as improved disease activity.

This adds evidence that we may be able to alter our gut bacteria with diet plus improve disease activity in autoimmune diseases! There is hope that diet could also possibly help other autoimmune diseases, such as lupus, in a similar way.

We absolutely need more research. Thanks to Dr. Guma and her team for helping to pave the way for more research on diet and autoimmune disorders.  Below are her results of the microbiome changes in the study.

What should be in an anti-inflammatory diet for lupus and other autoimmune diseases?

This is my commentary:

Some of the recommendations of Dr. Bustamante (first two pics above) have quite a bit of research supporting their use (eating foods high in omega-3, avoiding omega-6, eating prebiotics) in autoimmune diseases such as lupus.

However, others have significantly less evidence (for example, avoiding solanaceae, which is nightshade plants, and eating gluten-free).

I suspect the latter food groups were included since these changes "may possible reduce inflammation."

We all look forward to more studies in autoimmune disorders, such as lupus.

Comments Welcomed
Click on COMMENTS above

What have you found to be helpful in an anti-inflammatory diet?
What do you recommend for a beginner?
Do you recommend any particular books that you found to be most helpful?

produced by Kelli Roseta's "More Than Lupus"
​
The mission of the More Than Lupus Foundation is to provide programs and support for those living with lupus, advocate for their needs, and collaborate with other government and lupus organizations to strive toward improving quality of life, and ultimately finding a cure.  
​AuthorDon Thomas, MD author of "The Lupus Encyclopedia" and "​The Lupus Secrets"

​References: Under chapter 38