Obesity, a chronic low grade inflammation

Obesity associated health complications are thought to be in part due to the chronic low grade pro inflammation, that characterizes this disease.

flickr-Tony-Alter-8200130145_67a0ab58f4_k-INP obesityA quote from a recent article on obesity. In our clinic we regular see obese diabetic patients, suffering from chronic pain. Sometimes this pain resembles neuropathic pain, sometimes it is more of a Fibromyalgia sort.

Low Dose Naltrexone (LDN)

We gained some experience in treating chronic pain by using low dose naltrexone (LDN), sometimes together with low dose tramadol and would like to share this experience.

Without going into the pharmacological details, the quote above is followed with the conclusion:

  • Our observations that pro inflammatory factors increase calcium sensing receptor (CaSR) levels in adipocytes, and the reported ability of CaSR to elevate cytokine levels, open new aspects in the study of obesity inflammatory state pathophysiology, providing a potential novel therapeutic prevention and treatment target.[1]

No new treatments approaches yet, but…

Obesity is now generally considered as a chronic low-grade inflammatory state.[2][3][4] The literature supporting that obesity is linked to an overall low grade inflammation, and associated with chronic pain states, is overwhelming.

However, it did not yet result in new treatment approaches. It is interesting to note even in young children the enhanced inflammation can be found. And in line with this that weight loss in obese children reduced the low grade inflammation.[5][6]

In our clinic we work with low dose naltrexone (LDN). There is quite some literature supporting the analgesic effects of LDN and the anti-inflammatory activity of the same molecule.[7]

Other molecules have comparable action, although probably less intense, such as molecules in green tea.[8] Not uninteresting is the finding that LDN in obese animal models reduce the feeding behavior.[9]

Recently a high dose naltrexone regime, together with bupropion, reduced body weight in obese individuals, though the reduction was not overall very impressive.[10][11]

We think the dose selected (32 mg) is far to high up and creates many side effects. In our hands, even 1 mg naltrexone has biological actions, such as pain reduction and energy improvement, as well as improvement of quality of life.

LDN in chronic pain states in obesity

Due to the fact that LDN has anti-inflammatory actions as well as analgesic actions, we sometimes prescribe naltrexone in a low dose regime (1-2.5 mg, od) to patients. If the chronic pain state is difficult to treat, we might add a low dose regime of tramadol.

Between intake of both drugs 12 hours. The naltrexone up regulates our endogenous opiate receptors, and the up regulated state is a fact when tramadol enters the system. By cycling between and low dose opiate antagonist, LDN and 50 mg tramadol, an opiate agonist we enhance the analgesic effects. And side effects are minimal. Or, alternatively we combine LDN with Palmitoylethanolamide.

We feel this is a new inroad in treating obese patients suffering from severe pain, worthwhile exploring.

August 2010, Jan M. Keppel Hesselink, MD, PhD, revision march 2014
‘Obesity, a chronic low grade inflammation’

Watch our video’s about Neuropathy.

No new analgesics in 50 years

Psoriasis: a new innovative approach
Statins side effects: myalgia and myopathy
Glia modulators for neuropathic pain


[1] Cifuentes M, Fuentes C, Mattar P, Tobar N, Hugo E, Ben-Jonathan N, Rojas C, Martínez J. | Obesity-associated proinflammatory cytokines increase calcium sensing receptor (CaSR) protein expression in primary human adipocytes and LS14 human adipose cell line. | Arch Biochem Biophys. | 2010 Aug 15;500(2):151-6. Epub 2010 Jun 4.

[2] Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K. | Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. | Endocrinology. | 2007 Feb;148(2):868-77. Epub 2006 Nov 2.

[3] Snell-Bergeon JK, West NA, Mayer-Davis EJ, Liese AD, Marcovina SM, D'Agostino RB Jr, Hamman RF, Dabelea D. | Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH Case-Control study. | J Clin Endocrinol Metab. | 2010 Jun;95(6):2868-76. Epub 2010 Apr 6.

[4] von Schroeder HP, Coutts RD, Billings E Jr, Mai MT, Aratow M. | The changes in intramuscular pressure and femoral vein flow with continuous passive motion, pneumatic compressive stockings, and leg manipulations. | Clin Orthop Relat Res. | 1991 May;(266):218-26.

[5] Roth CL, Kratz M, Ralston MM, Reinehr T. | Changes in adipose-derived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. | Metabolism. | 2011 Apr;60(4):445-52. Epub 2010 May 24.

[6] Mauras N, Delgiorno C, Kollman C, Bird K, Morgan M, Sweeten S, Balagopal P, Damaso L. | Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children. | J Clin Endocrinol Metab. | 2010 Mar;95(3):1060-8. Epub 2010 Jan 8.

[7] Younger J, Mackey S. | Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. | Pain Med. | 2009 May-Jun;10(4):663-72. Epub 2009 Apr 22.

[8] Yun JM, Jialal I, Devaraj S. | Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers. | Br J Nutr. | 2010 Jun;103(12):1771-7. Epub 2010 Feb 23.

[9] Olszewski PK, Wirth MM, Grace MK, Levine AS, Giraudo SQ. | Evidence of interactions between melanocortin and opioid systems in regulation of feeding. | Neuroreport. | 2001 Jun 13;12(8):1727-30.

[10] Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. | Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. | Lancet. | 2010 Aug 21;376(9741):595-605. Epub 2010 Jul 29.

[11] Padwal R. | Contrave, a bupropion and naltrexone combination therapy for the potential treatment of obesity. | Curr Opin Investig Drugs. | 2009 Oct;10(10):1117-25.

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